George M. Church, Ph.D.

Producers of the popular online brain-training program Lumosity will collaborate with Harvard researchers to investigate the relationship between genetics and memory, attention, and reaction speed.Scientists at the Wyss Institute for Biologically Inspired Engineering and the Harvard Medical School Personal Genome Project (PGP) announced today a new collaboration with Lumos Labs that will leverage the unique resources and expertise of each.PGP-Lumosity Memory StudyWyss scientists plan to recruit 10,000 members from the PGP, which started in 2005 in the laboratory of George Church, a founding core faculty member of the Wyss Institute and a professor of genetics at Harvard Medical School (HMS). PGP participants make their genome sequences, biospecimens, and health care data publicly available for unrestricted research on genetic and environmental relationships to disease and wellness. The Wyss researchers will use a set of cognitive tests from Lumos Labs’ NeuroCognitive Performance Test, a brief, repeatable, online assessment to evaluate participants’ memory functions, including object recall, object pattern memorization, and response times.Church’s team and HMS postdoctoral fellows Elaine Lim and Rigel Chan will correlate extremely high performance scores with naturally occurring variations in the participants’ genomes. “Our goal is to get people who have remarkable memory traits and engage them in the PGP. If you are exceptional in any way, you should share it, not hoard it,” Church said.

Plants engineered with a specific biosensor can signal when they detect a molecule of interest, such as the human hormone progesterone or the drug digoxin, according to a team of researchers at Harvard’s Wyss Institute and Harvard Medical School (HMS).

Synthetically engineered biosensors, which can be designed to detect and signal the presence of specific small-molecule compounds, have already unlocked potential applications, such as fuel, plastics, and pharmaceuticals. Until now, however, scientists have been challenged to leverage biosensors for use in eukaryotic cells, which comprise yeast, plants, and animals.

Led by Wyss core member George Church, a team of researchers developed a new method for engineering a broad range of biosensors to detect and signal virtually any desired molecule using living eukaryotic cells. The team reported its findings in the journal eLife.

“Biosensors that can tell you about their environment are extremely useful for a broad range of applications,” said Church, the Robert Winthrop Professor of Genetics at HMS. “You can imagine if they were used in agricultural plants, they can tell you about the condition of the soil, the presence of toxins or pests that are bothering them.”

Super-productive factories of the future could employ fleets of genetically engineered bacterial cells, such as common E. coli, to create valuable chemical commodities in an environmentally friendly way. By leveraging their natural metabolic processes, bacteria could be reprogrammed to convert readily available sources of natural energy into pharmaceuticals, plastics, and fuel products.

“The basic idea is that we want to accelerate evolution to make awesome amounts of valuable chemicals,” said Wyss Institute core faculty member George Church, who is a pioneer in the converging fields of synthetic biology, metabolic engineering, and genetics. Church is the Robert Winthrop Professor of Genetics at Harvard Medical School and professor of health sciences and technology at Harvard and MIT.

Critical to this process of metabolically engineering microbes is the use of biosensors. Made of a biological component — such as a fluorescent protein — and a “detector” that responds to the presence of a specific chemical, biosensors act as the switches and levers that turn programmed functions on and off inside the engineered cells. They also can be used to detect which microbial “workers” are producing the most voluminous amounts of a desired chemical. In this way, they can be thought of as the medium for two–way communication between humans and cells.

The new “Disruptive” podcast from the Wyss Institute for Biologically Inspired Engineering at Harvard University explores what motivates researchers and how they envision our future as it might be impacted by their disruptive technologies.

In its inaugural episode, “Disruptive” host and 1969 Harvard alumnus Terrence McNally spoke with Wyss core faculty members Pamela Silver and George Church about the changes that can be made to an organism’s genome. Silver and Church explained how, with today’s breakthroughs in technology, such modifications can be conducted more cheaply, efficiently, and effectively than ever before.

Researchers around the world are programming microbes to treat wastewater, generate electricity, manufacture jet fuel, create hemoglobin, and fabricate new drugs. What sounds like science fiction to most of us might be a reality in our lifetimes: the ability to build diagnostic tools that live within our bodies, or find ways to eradicate malaria from mosquito lines, or possibly even make genetic improvements in humans that are passed down to future generations.

Silver, the Elliott T. and Onie H. Adams Professor of Biochemistry and Systems Biology at Harvard Medical School (HMS), and Church, the Robert Winthrop Professor of Genetics at HMS, also revealed the high-impact benefits of their synthetic biology work, and discussed their careful consideration and prevention of unintended consequences in this new age of genetic engineering.

A team of researchers led by Harvard geneticist George Church at the Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) has made big strides toward a future in which the predominant chemical factories of the world are colonies of genetically engineered bacteria.

In a new study, scientists at the Wyss Institute modified the genes of bacteria in a way that lets them program exactly what chemical they want the cells to produce — and how much — through the bacteria’s metabolic processes. The research was reported in the Proceedings of the National Academy of Sciences (PNAS).

The concept of metabolic engineering, or manipulating bacteria to synthesize useful chemicals, is not new to synthetic biologists. However, what these recent findings promise is up to a 30-fold increase in chemical output. This demonstrates a technique that allows scientists to tap an almost endless list of chemicals they can produce using any type of bacteria, such as the common E. coli, which was used in the study. Most promising, the production timescale is nearly 1,000-fold faster than the methods currently used for metabolic engineering.

“This advance has implications for pharmaceutical, biofuel, and renewable chemical production,” said Wyss Institute Founding Director Donald Ingber. “By increasing the production output by such a huge factor, we would not only be improving current chemical production but could also make economical production of many new chemicals attainable.”

Genome engineering technologies have revolutionized genetics, biotechnology, and medical research.  We may soon be able to alter not just domesticated species, but entire wild populations and ecosystems.  Why, when and how might we use these novel methods to reshape our environment?

The story begins with a new technology that has made the precise editing of genes in many different organisms much easier than ever before.  The so-called “CRISPR” system naturally protects bacteria from viruses by storing fragments of viral DNA sequence and cutting any sequences that exactly match the fragment.  By changing the fragments and delivering the altered system into other organisms, we can cut any given gene.  If we also supply a DNA sequence that the cell can use to repair the damage, it will incorporate this new DNA, precisely editing the genome.  When performed in the cells that give rise to eggs or sperm, these changes will be inherited by future generations.  Because most altered traits don’t improve and may even decrease the organism’s ability to survive and reproduce, they generally can’t spread through wild populations.

People who give blood or other tissues for research should be able to track their use through the scientific process to see the data their activities or samples generate, Harvard University scientists said.

The standard one-way flow of information creates an unequal relationship that blocks participants’ ability to hold scientists accountable for how the data is used, Harvard genetics researchers George Church and Jeantine Lunshof said in a policy paper written with Barbara Prainsack from King’s College London. The paper will be published tomorrow in the journal Science.

Biobanks hold vast stores of information about individuals’ genes, tissues, and illnesses, and research subjects should have some right to see where their data is kept and how it’s used, the authors said. The current system is like a financial bank that won’t allow customers to verify that their money is in an account, Lunshof, a visiting fellow in genetics at Harvard Medical School in Boston, said in a telephone interview.

“When you donate your data or material to a researcher, it’s actually quite logical to think you’d get an acknowledgment of it and the opportunity to see what you gave them,” Lunshof said. “But right now it is a one-way transaction, and anything you contribute goes into a black hole.”

Church and Lunshof are researchers in the Personal Genome Project, a Harvard-based program that returns the results of full-genome sequencing to individuals. The project’s website explains that participants may receive unexpected information about their health or genetic background.

In early December, Harvard geneticist George Church addressed a crowd of about 150 life science professionals gathered at Google’s Cambridge office and asked how many of them had had their genomes sequenced. Not a single person raised a hand.

Church appeared to have expected the negative response, even at an event where people paid $150 to hear about the future of personalized health care. What baffled him was why? Genome sequencing’s low adoption rate is “one of the greatest paradoxes of our time,” Church said.

“I wouldn’t wait,” he said. “I didn’t wait. I was the fifth person on the planet to get sequenced.”

Ten years after completion of the Human Genome Project made it possible to paint a full genetic portrait of anyone in the world, sequencing remains far outside the mainstream. The process entails documenting each of the body’s 3.2 billion nucleotides — the building blocks of DNA — which are expected to appear in a certain pattern, just like the alphabet. Variations from the normal pattern of nucleotides can signal that a person is likely to develop a certain disease later in life, or is a carrier who could pass a health problem on to a child.

As Supreme Court Justice Elena Kagan questioned Myriad Genetics’ attorney about patenting genes, Chris Hansen rejoiced.

The attorney said that yes, genes should be patentable. But it was only under the pressure of further questions that he said that chromosomes, too, should be patentable, and — more reluctantly still — organs such as kidneys.

“It was all I could do to not leap out of my chair and go, ‘Yaaay!’ ” Hansen said of the spring hearing.

To Hansen, the American Civil Liberties Union (ACLU) lawyer who led the lawsuit against Myriad Genetics’ patents of two human breast cancer genes, BRCA1 and BRCA2, the exchange augured well for the case’s outcome. The line of questioning seemed to bolster the ACLU’s argument that the genes were a product of nature, like a kidney, and so by law, not patentable. In isolating the genes for breast cancer, it argued, Myriad invented nothing that wasn’t already there.

That reasoning ultimately won the day. In its July decision, the Supreme Court ruled unanimously that human genes were not patentable, overturning common practice both in the biotech industry and at the U.S. Patent and Trade Office, which by the time of the case had issued patents for 20 percent of human genes. The decision also found, however, that synthetic copies of genes, called cDNA, were patentable.

In 2008, a group of prominent scientists and entrepreneurs announced, after careful consideration, that they would make their genome sequences public, marking the launch of the Personal Genome Project (PGP). The “open source” genomics effort sought to make the genomes and medical histories of 100,000 people available for anyone to use. It was started by George Church, a genomicist at Harvard Medical School in Boston who was among the first 10 participants, or the “PGP-10.”

Now Church is taking his open-access genome model global. At a predictably packed press conference on 6 November, he announced the launch of a UK edition, and that a European franchise is on the way for 2014. A Canadian PGP started enrolling volunteers in December 2012.

The UK-PGP is aiming for another 100,000 participants. Stephan Beck, a genomicist at University College London leading the effort, says he is one of the 400 already on the waiting list. They plan to sequence 50 genomes in the first year.

In the five years since it started, the US edition has released 200 genomes and more limited genetic data on another 500, with a waiting list in the thousands. But Church expects growth to be exponential, once sequencing costs fall sufficiently.

Reprogramming bacteria to produce proteins for drugs, biofuels, and more, has long been part of the job for bioscientists, but for years they have struggled to get those bugs to follow orders.

Those days may be over. It turns out that a hidden feature of the genetic code controls how much of the desired protein bacteria produce, a team from the Wyss Institute for Biologically Inspired Engineering at Harvard reported in today’s online issue of Science.

The findings could be a boon for biotechnologists, and help synthetic biologists reprogram bacteria to make new drugs and biological devices.

By combining high-speed “next-generation” DNA sequencing and DNA synthesis technologies, Sriram Kosuri, a Wyss Institute staff scientist, George Church, a core faculty member at the Wyss Institute and professor of genetics at Harvard Medical School, and Daniel Goodman, a Wyss Institute graduate research fellow, found that using more rare words, or codons, near the start of a gene removes roadblocks to protein production.

When genomics pioneer George Church recently announced that he and his team at Harvard’s Wyss Institute for Biologically Inspired Engineering will vie in a September 2013 competition to rapidly and accurately sequence 100 whole human genomes at a cost of $1,000 or less each, he did not say which technology they would use to do it. That’s because quite possibly it has not yet been invented.

Church’s Harvard Medical School lab is known for developing or collaborating on some of today’s most advanced DNA analysis tools, including the Polonator instrument and a recent upgrade, “LFR,” or long fragment read sequencing—recently shown to be highly accurate and cost-effective—and nanopore sequencing, which has been licensed and commercialized by several companies. Since the dawn of the human genome project, Church and his colleagues have been instrumental in bringing the cost of DNA sequencing down one-million fold. But genomics technology continues to evolve so quickly that it’s impossible to predict what the state-of-the-art will look like nine months from now.

So far, Church’s team has only one opponent for the $10 million Archon Genomics X Prize. Corporate giant Life Technologies entered the contest with its Ion Proton Sequencer, invented by the team’s leader Jonathan Rothberg.

George Church is a professor of genetics at Harvard University’s Wyss Institute for Biologically Inspired Engineering, and also co-author of the book Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves in DNA. With a title like that, it’s only fitting that the book was used to break the record that it recently did – Church led a team that encoded 70 billion html copies of the book in DNA. That’s 1,000 times more data than the previous record.

Using next-generation sequencing technology, Church’s team successfully stored the text, images and formatting of the book onto “standalone DNA” obtained from commercial DNA microchips. This was achieved by assigning the four DNA nucleobases the values of the 1s and 0s in the existing html binary code – the adenine and cytosine nucleobases represented 0, while guanine and thymine stood in for 1.

The density at which the data was stored is truly impressive, coming in at 5.5 petabits (one million gigabits) per cubic millimeter. At that rate, according to research partner Sriram Kosuri, the entire amount of digital data created worldwide in one year could theoretically be stored on just four grams of DNA.

Two Harvard scientists have produced 70 billion copies of a book in DNA code –and it’s smaller than the size of your thumbnail.

Despite the fact there are 70 billion copies of it in existence, very few people have actually read the book Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves in DNA, by George Church and Ed Regis. The reason? It is written in the basic building blocks of life: Deoxyribonucleic acid, or DNA.

Church, along with his colleague Sriram Kosuri, both molecular geneticists from the Wyss Institute for Biologically Inspired Engineering at Harvard, used the book to demonstrate a breakthrough in DNA data storage. By copying the 53,000 word book (alongside 11 jpeg images and a computer program) they’ve managed to squeeze a thousand times more data than ever previously encoded into strands of DNA, as reported in the August 17 issue of the journal Science. (To give you some idea of how much information we’re talking about, 70 billion copies is more than three times the total number of copies for the next 200 most popular books in the world combined.)

Although George Church’s next book doesn’t hit the shelves until Oct. 2, it has already passed an enviable benchmark: 70 billion copies — roughly triple the sum of the top 100 books of all time.

And they fit on your thumbnail.

That’s because Church, a founding core faculty member of the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Robert Winthrop Professor of Genetics at Harvard Medical School, and his team encoded in DNA the book, Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves in DNA, which they then decoded and copied.

Biology’s databank, DNA has long tantalized researchers with its potential as a storage medium: fantastically dense, stable, energy-efficient and proven to work over a timespan of some 3.5 billion years. While not the first project to demonstrate the potential of DNA storage, Church’s team married next-generation sequencing technology with a novel strategy to encode 1,000 times the largest amount of data previously stored in DNA.

The team reports its results in the Aug. 17 issue of the journal Science

Forget flash – the computers of the future might store data in DNA. George Church of the Wyss Institute at Harvard University and colleagues have encoded a 53,400-word book, 11 JPG images and a JavaScript program – amounting to 5.27 million bits of data in total – into sequences of DNA. In doing so, they have beaten the previous record set by J. Craig Venter’s team in 2010 when they encoded a 7920-bit watermark in their synthetic bacterium.

DNA is one of the most dense and stable media for storing information known. In theory, DNA can encode two bits per nucleotide. That’s 455 exabytes – roughly the capacity of 100 billion DVDs – per gram of single-stranded DNA, making it five or six orders denser than currently available digital media, such as flash memory. Information stored in DNA can also be read thousands of years after it was first laid down.

Until now, however, the difficulty and cost involved in reading and writing long sequences of DNA has made large-scale data storage impractical. Church and his team got round this by developing a strategy that eliminates the need for long sequences. Instead, they encoded data in distinct blocks and stored these in shorter separate stretches.

The strategy is exactly analogous to data storage on a hard drive, says co-author Sriram Kosuri, where data is divided up into discrete blocks called sectors.

The Wyss Institute for Biologically Inspired Engineering at Harvard University announced today that one of its core faculty members, George Church, has been elected a member of the National Academy of Engineering (NAE) for contributions to human genome sequencing technologies and DNA synthesis and assembly. Election to the National Academy of Engineering is among the highest professional distinctions accorded to an engineer.

Q&A with the Harvard geneticist.

Earlier this year, I had breakfast with George Church, professor of genetics and director of the Center for Computational Genetics at Harvard Medical School. (Click here to read my profile of Church in the New York Times.)

A pioneer in developing DNA sequencing technologies, and in researching everything from epigenetics and microbiomics to synthetic biology, Church has co-founded or advises over 20 companies. He also has launched the Personal Genome Project with a goal of sequencing the complete genomes of 100,000 volunteers.

When I asked Church what he was most excited about right now, he answered without hesitation: “I’m thinking a lot about using regeneration as the key to treatments and keeping people healthy.”

The power to edit genes is as revolutionary, immediately useful, and unlimited in its potential as was Johannes Gutenberg’s printing press. And like Gutenberg’s invention, most DNA editing tools are slow, expensive, and hard to use — a brilliant technology in its infancy. Now, Harvard researchers developing genome-scale editing tools as fast and easy as word processing have rewritten the genome of living cells using the genetic equivalent of search and replace — and combined those rewrites in novel cell strains, strikingly different from their forebears.

“The payoff doesn’t really come from making a copy of something that already exists,” said George Church, a professor of genetics at Harvard Medical School who led the research effort in collaboration with Joe Jacobson, an associate professor at the Media Lab at the Massachusetts Institute of Technology. “You have to change it — functionally and radically.”

It is perhaps fitting that the new prototype of a machine Harvard Medical School geneticist George Church developed to “mass produce” new genes looks a little like a high-end stove. (Linked Photo courtesy of Marie Wu.)  “Cooking,” as one lab director once told me, is basically what lab researchers do. They cook with genes.

The MAGE (multiplex automated genome engineering device) will allow scientists to cook exponentially faster.

One of the major obstacles to genetic engineering has been the cost and labor involved in changing even a small number of genes in an organism. The most basic of traits (for example, the redness of a tomato) can depend on a complicated network of several sequences of genetic code. If any progress is to be made in changing multiple traits in organisms (especially the kind that scientists and entrepreneurs hope can be used to synthetically ‘grow’ alternative forms of fuel), then they will need to come up with a more efficient way to do it.

One way, some have suggested, is to let Darwin do the work. And that’s where the MAGE comes in.

The Wyss Institute for Biologically Inspired Engineering at Harvard University announced today that one of its core faculty members, George Church, has been elected a member of the National Academy of Sciences (NAS) in recognition of his distinguished and continuing achievements in original research. Membership in the academy is one of the highest honors accorded a scientist or engineer.